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Biogenesis of yeast M ia40 – uncoupling folding from import and atypical recognition features
Author(s) -
Chatzi Afroditi,
Sideris Dionisia P.,
Katrakili Nitsa,
Pozidis Charalampos,
Tokatlidis Kostas
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12482
Subject(s) - biogenesis , biology , intermembrane space , microbiology and biotechnology , mitochondrial intermembrane space , translocon , biophysics , plasma protein binding , sequence (biology) , oxidoreductase , folding (dsp implementation) , mitochondrial biogenesis , biochemistry , mitochondrion , enzyme , gene , chromosomal translocation , escherichia coli , bacterial outer membrane , engineering , electrical engineering
The discovery of the mitochondrial intermembrane space assembly ( MIA ) pathway was followed by studies that focused mainly on the typical small substrates of this disulfide relay system and the interactions between its two central partners: the oxidoreductase M ia40 and the FAD ‐protein E rv1. Recent studies have revealed that more complex proteins utilize this pathway, including M ia40 itself. In the present study, we dissect the M ia40 biogenesis in distinct stages, supporting a kinetically coordinated sequence of events, starting with (a) import and insertion through the T im23 translocon, followed by (b) folding of the core of imported M ia40 assisted by the endogenous M ia40 and (c) final interaction with E rv1. The interaction with endogenous M ia40 and the subsequent interaction with E rv1 represent kinetically distinguishable steps that rely on completely different determinants. Interaction with M ia40 proceeds very early (within 30 s) and is characterized by no C ys‐specificity, an increased tolerance to mutations of the hydrophobic substrate‐binding cleft and no apparent dependence on glutathione as a proofreading mechanism. All of these features illustrate a very atypical behaviour for the M ia40 precursor compared to other substrates of the MIA pathway. By contrast, interaction with E rv1 occurs after 5 min of import and relies on a more stringent specificity.